Supersaturated calcium gluconate solution



Patented Apr. 18,1933

ARTEUB STOLL ANDEBNS'I ROTHLIN, OF BASEL, ASSIGFOBB 'ro FIRE F CHEMICAL WORKS FOBHERLY SANDOZ," OF BASED, v

PATENT oFF cEi SUPEBSATURATED GALCIUK GLUCONA'IE SOLUTION Io Drawing. Application med October 18, 1928, Serial no. 400,157, and in Germany October 39. 1980.

to such a heatlng'operation that after cooling no further crystallization takes place. Under these conditions, the expected salting action of the additions does not occur.

This invention is very important for the therapy, as it allows to administer by way of the parenteral injection, all sorts of injection-preparations together with the calcium gluconatesolutions, the last being less dangerous or irritating compared to calcium chloride. The calcium gluconate fulfils in many, cases the requirement of helping or smoothing the therapeutical action of the admixtures.

To clearly show the great variability of our new recess, the followin com ounds which may e added to the calcium g uconate solutions are cited: Metal salts of the alkali and earth-alkali group, such as sodium chloride, sodium salicylate, sodium glycerophosphate, sodium cacod late, sodium cholate, sodium nucleinate, lit ium citrate. calcium glycerophosphate, strontium ,gluconate; salts of heavy metals such as cadmium gluconate, iron gluconate, the'usual combinations of iron with arsenic, nickel gluconate, suitable manese, arsen-, antimony, mercuryand silver compoundsaJbismuth further alkaloids,

for instance suita le salts of atropin, quinine,

uinoline-derivatives like halogen-oxy-quinolmesulfonic acids, and also 5-alkoxy-8-aminoquinolines and their N substitution products, salts of codeine, cotamine, emetine, ephea drine, ergotamine, hydrastine, Zpapaverine,

therein, after having introduced same into containers adapted to be hermetically closed,

sary in all cases to heat the sealed 1 pilocarpine, sparteine, st chnine; cafieine and theobromine and their ouble compounds with sodiumbenzoateor salicylate; dyestufis which are used inthe chemical-therapy like for-instance Methylene blue, Trypan blue, acridine-dyestufis; natural gluoosides such as digitoxine, strophantine; also soluble compounds of substituted barbituric acids and of antipyretica, further local aneesthetica' of the aminobenzoic acid series, and also a series of diflerent compounds which are used in the injection therapy like glycerine, glucose, gelatine. paraldehyde, hexamethylentetramine, thyroxine, pyridine-beta carbonic acid diethylamide pentamethylenetetrazol, l- U ated cyclic hetones, camphor and most of e sterines, for instance ergosterine and others.

Unsuitable are such additions which possess too little solubility or which react with calcium gluconate and produce diflicultly I. soluble compounds, and also such which show a loss of their therapeutical action when heated at tem ratuies which are my to' stabilize e supersaturated calcium gluconate solutions.- We have further found that it is not necesat a temperature of 100 0. Sometimes one or several heating operations at fill- G. are sufiicient to prepare stable .1 r-saturah' 0t? ed calcium gluconate solutions. i is very i important especially in the case when heat sensitive com unds are used together with the calcium g neonate. The following examples illustrate the in vention:

Example 1.200 g. of calcium glucouate are dissolved in 1500 cc. of. hot water, g. of pure sodium chloride are added, and the solution is then diluted to 2000 cc. The hot j solution thus obtained is then filled in'am- I scales, which, after sealing, are heatedtwice uring two hours at intervals of a day at 0. Thus, the solution in the ampoules is stabilized and does not; even utter several months, show any precipitation.

Ext-ample 2.--10 g. of calcium gluconete and 20 g. of sodiumsalicylate are dissolved in cc. of hot water and filled in ampou'les,

which, after sealing, are heated three times no clear; this would not be the case of ampoules which have not been heated and where a crystallization of calcium gluconate takes place very soon.

Example-3.-Equal parts of magnesium gluconate and calcium gluconate are dissolved in such a quantity of hot water, that the solution when cooled down, contains in 10 cc. one gram of each of the salts. The hot solution is filled up in ampoules, which are heated twice during two hours at intervals of a day at 95 C. The solution, when cooled, does not give an precipitate.

Example 4.- stable calciumand strontium gluconate solution may be prepared if 5 g. of calcium gluconate and 5 g. of strontium gluconate are dissolved in 100 cc. of hot water, the hot solution poured into ampoules which are further heated at 80-90 C. one or several times, until the solution remains perfectly clear after long storage.

Example 5.Similarly to the above cited example,- a stable solution may be prepared by dissolving 1 gram of cadmium gluconate or nickel gluconate or iron gluconate in 100 cc. of a hot 10 per cent solution of calcium gluconate, filling up thehot solution in ampoules and heating same as described.

Example 6.0.5 g. of tartar emeticare dissolved in 100 cc. of a 10per cent solution of calcium gluconate. The hot solution is introduced into ampoules or bottles which are then hermetically closed and heated several times at short intervals for one or two hours at 60-90 C. The solution remains perfectly clear after cooling.

' Example 7.-0.3 g. of codeine hydrochloride or 5.0 g. of quinine hydrochloride or'2.0 g. of

caffeine or 0.2g. of cotarnine hydrochloride are dissolved in 100 cc. of ahot 10 per cent solution of calcium gluconate,the hotsolution is then filled up into suitable containers, which are then hermetically closed and heated several times during one hour at 6070 C. at

intervals of a day. The solutions do not show any crystallization after cooling down, whilst containers which contain the same solution and which have not been heated soon show very strong precipitations of calcium glu-.

conate.

Example 8.7.5 g. V of cafleine-sodium salicylate dissolved in 100 cc. of a hot 10% solution of calcium gluconate give stable solutions when proceeded as described above.

Example 9.-1.0 g. of medicinal Methylene blue, or 1.0 g. of Trypan blue or 20 g. of 2- ethoxy-6: 9-1diamino acridinum lactate are dissolved in 100 cc. of a hot 10 per cent solution of calcium gluconate, and filled when hot into suitable containers, for instance bottles even after longstorage do not show any precipitation.

,amineleucinolester are dissolved in 100 cc. of.

a hot 10 per cent solution of calcium gluconate. After heating two or three times at a temperature of 6070 C. for one hour, the solution is stabilized. 7

Example 1].Solutions prepared by dissolving in 100 cc. of a 10 per cent solution of calcium gluconate for instance 10.0 g. of hexamethylenetetramine or 10 g. of glycerine or 10 g. of gelatine or even 30 g. of glucose, may be stabilized, when prepared as described above.

What we claim is As new composition of matter, clear, stable, sterile and supersaturated aqueous calcium gluconate solutions, containing 410% of calcium gluconate and such therapeutically useful compounds, that are heat insensitive and incapable of reacting with calcium gluconate,

our names this 7th day of October, 1929.

ARTHUR STOLL. ERNST ROTHLIN.

or ampoules, which after being hermeticallyv closed are heated several times at a temperature of 5095 C. The solutions thus obtained 

